Project Summary Our behavior is inextricably linked to a wide range of rewards, from economic incentives (e.g., monetary compensation) to social incentives (e.g., praise from a peer). Receipt of reward promotes learning, evokes pleasure, and increases brain activity within the striatum?a key structure within the reward circuit. Although striatal responses to reward are correlated with learning and positive emotions, it remains unclear how the experience of reward in humans is causally linked to the striatum. Indeed, the striatum is buried deep inside the brain, making it inaccessible to approaches that assess causality via noninvasive brain stimulation. The goal of this project is to determine whether reward-related responses within the striatum can be influenced via stimulation applied to cortical connections. We will use a novel form of noninvasive neuromodulation, that we coined short-term transcranial alternating current stimulation (st-tACS) to prefrontal cortex while participants engage in reward tasks that reliably evoke activation within the striatum. We will address two specific aims. In our first aim, we will investigate whether st-tACS alters striatal responses to reward and pleasure associated with a simple guessing game. In our second aim, we will investigate whether st-tACS alters striatal responses to reward and learning. We hypothesize that st-tACS applied to prefrontal cortex will increase striatal responses to reward, an effect that will be tied to increased pleasure (Aim 1) and increased learning (Aim 2). These findings would therefore establish causal links between the human striatum and reward. Moreover, remote modulation of the human striatum could expand the purview of noninvasive brain stimulation approaches, potentially establishing a foundation for new therapeutic directions for psychopathologies characterized by aberrant responses to reward.